Background/Purpose

Interleukin-6 (IL-6) is considered a key cytokine in the pathogenesis of rheumatoid arthritis (RA). Tocilizumab (TCZ) is a monoclonal antibody which binds to membrane-bound and soluble forms of human IL-6 receptor, and has proved to be effective in the treatment of RA. In the standard protocol for RA, TCZ is administered intravenously every four weeks. However, given that the impact of IL-6 presumably differs among patients, treatment might be optimized by shortening or prolonging the administration interval of TCZ. Here, we evaluated the usefulness of modifying the protocol based on the treat-to-target concept in daily practice.

Methods

We retrospectively surveyed all 453 patients treated with TCZ (8mg/kg) at our institution between 2008 and 2014. Patients administered TCZ at an interval of ≤ 3 weeks or ≥ 5 weeks were analyzed as the shortened or prolonged interval group, respectively. Clinical information, including disease activity, was collected and statistically analyzed.

Results  

A) Patients administered TCZ at a shortened interval (administration interval ≤ 3 weeks)
Among 453 patients, 25 (5.5%) were administered TCZ at a shorter interval due to insufficient effectiveness after administration at a 4-week interval for a median of 33.8 weeks. Disease activity was significantly improved after two administrations at this shortened interval, with disease activity score (DAS) 28 changing from 5.10 to 3.40 (p<0.05). Among these 25 cases, interval could be returned to 4 weeks in 15. In contrast, the remaining 10 required continuous administration at a shortened interval for more than 1 year due to exacerbation of RA activity on return to a 4-week interval.

B) Patients administered TCZ at a prolonged interval (administration interval ≥ 5 weeks)
 Sixty-three patients (13.9%) were administered TCZ at a prolonged interval, after having achieved remission after a median of 70.0 weeks at a 4-week interval. The prolonged interval ranged from 5 to 8 weeks. Of these 63 patients, 48 (76.2%) were able to continue TCZ administration at a prolonged interval for more than 1 year, while 15 (24.8%) required returning to a 4-week interval due to exacerbation of RA activity after a median of 51.1 weeks at a prolonged interval. All 15 cases achieved low disease activity equivalent to the original level before interval prolongation.

Conclusion

Our study highlighted the importance of administration interval in the effectiveness of TCZ in RA. Adjustment of interval according to disease activity in individual patients is a promising way to optimize treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/utility-of-adjustment-of-administration-interval-in-tocilizumab-in-rheumatoid-arthritis/